13 variant loci were filtered in the monozygotic twins
In this study, blood sample from 9 pairs of monozygotic twins with psoriasis discordance was analyzed by whole genome sequencing. We obtained 13 variants loci, such as kinesin light chain 1 (KLC1, c.216A > G), protein kinase C epsilon (PRKCE,c.240T > C), Multiple epidermal growth factor-like domains 6 (MEGF6, c.96 A > G), Cell adhesion molecule 2 (CADM2, c.263 A > G), Multiple epidermal growth factor-like domains 11 (MEGF11, c.80 T > G), Neural cell adhesion molecule 2 (NCAM2, c.236 G > T), Dipeptidyl peptidase like 6 (DPP6, c.174 G > T), Myosin heavy chain 14 (MYH14, c.461 T > C), Serine palmitoyltransferase long chain base subunit 3 (SPTLC3, c.481 T > C), FA complementation group C (FANCC, c.134 C > T), DENN domain containing 5B (DENND5B, c.96 A > G) Junctophilin 2 (JPH2, c.195 T > G) and RNA polymerase II associated protein 3 (RPAP3, c.146 C > G) (Table 1). Interestingly, all of the 13 above mentioned variant loci were found only in the normal homozygote, but none of them in psoriatic homozygote. Variant exist in normal populations, indicating their potential prevention to psoriasis.
Table 1
Thirteen mutant loci in 9 pairs of monozygotic twins
Chromosome | SNP | variants loc | Gene |
Chr1 | rs2821008 | c.96 A > G | MEGF6 |
Chr3 | rs10511083 | c.263 A > G | CADM2 |
Chr15 | rs72742862 | c.80 T > G | MEGF11 |
Chr20 | rs761206 | c.195 T > G | JPH2 |
Chr21 | rs2826733 | c.236 G > T | NCAM2 |
Chr2 | rs3738896 | c.240 T > C | PRKCE |
Chr7 | rs35660473 | c.174 G > T | DPP6 |
Chr9 | rs2121200 | c.134 C > T | FANCC |
Chr12 | rs11168200 | c.146 C > G | RPAP3 |
Chr19 | rs788336 | c.461 T > C | MYH14 |
Chr20 | rs6041870 | c.481 T > C | SPTLC3 |
Chr12 | rs1259410 | c.288 T > C | DENND5B |
Chr14 | rs861536 | c.216 A > G | KLC1 |
The variation frequency of PRKCE and KLC1 were lower than normal individuals
Among 614 loci in 282 psoriasis patients, 240 loci in protein kinase C epsilon (PRKCE) were mutated (c.240T > C), and the variation frequency in patients with psoriasis (36.3%) was significantly lower than that in normal Asian individuals (47.7%, P < 0.05). Moreover, 216 loci in kinesin light chain 1 (KLC1) were mutated (c.216A > G), and the variation frequency in patients with psoriasis (1.2%) was significantly lower than that in normal Asian individuals (98.1%, P < 0.01). In addition, the mean variation frequencies of the genes MEGF6 ( 20.2% vs 25.9%), CADM2, (71.4% vs 86.1%), MEGF11(59.2% vs 61.8%), NCAM2(32.4% vs 33.6%), DPP6 (81.2% vs 83.9%), MYH14 (17.7% vs 22.0%), SPTLC3(64.5% vs 66.1%), FANCC (4.4% vs 4.60%) and DENND5B (0.53% vs 0.6%) were lower in patients with psoriasis than in normal individuals, though all of P value was higher than 0.05. However, the variation frequencies of JPH2 (86.1% vs 85.12%) and RPAP3 (28.0% vs 26.9%) were higher in patients with psoriasis than in normal individuals (Fig. 1).
Occurrence of psoriasis and its relationship with the sociodemographic characteristics of participants
Medical history, the PASI score and family history were used to clarify the different clinical subtypes. Therefore, the relationship between medical history, the PASI score, family history and variant genes was investigated. CADM2(χ2 = 9.29, P < 0.05), JPH2(χ2 = 8.47, P < 0.05), SPTLC3 (χ2 = 20.65, P < 0.01) was significantly different between patients with different medical histories(Fig. 2). Analysis of the PASI score revealed a significant association with variation in MEGF6 (χ2 = 6.06, P < 0.05). Next, we further analyzed the relationship between family history and variant genes and found that CADM2(χ2 = 6.08, P < 0.05), JPH2(χ2 = 10.98, P < 0.01), SPTLC3 (χ2 = 8.51, P < 0.01) was significantly associated with family history, suggesting that the variation in CADM2,JPH2, SPTLC3 may be the risk factor for psoriasis in individuals who have a family member with psoriasis.
Univariate and multivariate analysis of family history on disease characteristics
For research purposes, we rearranged the population data and divided individuals with psoriasis into two groups, as shown in Table 2. Research has shown that with the extension of time, new mutations will emerge and old ones will be repaired. Therefore, to eliminate the impact of time on mutation gene, we divided into two groups based on medical history and then compare different PSAI and family history of patients. In the under 20 years medical history group and over 20 year medical histroy group, we analyzed the relationship between gender, age, PASI, family history and gene mutation. For the comparison of family histroy of two group, we found that CADM2(χ2 = 5.89,94.87% vs 76.56%, p<0.05) was a risk factor for having family histroy with type Ⅰ psoriasis. Similarly when compared to patients with under 20 years medical history group and over 20 year medical histroy group, there were differences in MEGF6(χ2 = 3.86,39.52% vs 22.5%, p<0.05) according to PASI of type Ⅰ psoriasis.
Table 2
Chi-square test the PASI and family history in patients with different medical histories
| Medical history<20 | Medical history ≥ 20 |
| PASI ≤ 10 | PASI >10 | χ2 | Family history (YES) | Family history (NO) | χ2 | PASI ≤ 10 | PASI >10 | χ2 | Family history (YES) | Family history (NO) | χ2 |
MEGF6 | 39.52% | 22.50% | 3.83 | 41.03% | 31.25% | 1.02 | 40.24% | 22.22% | 3.58 | 36.84% | 36.92% | 0.00 |
CADM2 | 83.87% | 72.50% | 2.55 | 94.87% | 76.56% | 5.89 | 73.17% | 75.00% | 0.04 | 71.05% | 73.85% | 0.09 |
MEGF11 | 87.10 | 85.00% | 0.11 | 76.92% | 89.06% | 2.72 | 79.27% | 80.56% | 0.03 | 71.05% | 84.62% | 2.72 |
JPH2 | 99.19% | 95.00% | 2.96 | 100.00% | 95.31% | 1.88 | 95.12% | 91.67% | 0.54 | 97.37% | 92.31% | 1.12 |
NCAM2 | 57.26% | 52.50% | 0.28 | 56.41% | 56.25% | 0.00 | 52.44% | 61.11% | 0.76 | 63.16% | 50.77% | 1.49 |
PRKCE | 49.19% | 42.50% | 0.54 | 33.33% | 51.56% | 3.26 | 57.32% | 61.11% | 0.15 | 63.16% | 55.38% | 0.60 |
DPP6 | 94.35% | 92.50% | 0.18 | 92.31% | 98.44% | 2.44 | 91.46% | 97.22% | 1.31 | 89.47% | 93.85% | 0.64 |
FANCC | 8.06% | 10.00% | 0.15 | 10.26% | 6.25% | 0.54 | 9.76% | 5.56% | 0.57 | 7.89% | 9.23% | 0.05 |
RRAP3 | 44.35% | 57.50% | 2.10 | 51.28% | 50.00% | 0.02 | 48.78% | 41.67% | 0.51 | 39.47% | 49.23% | 0.92 |
MYH14 | 31.45% | 42.50% | 1.64 | 33.33% | 28.13% | 0.31 | 31.71% | 22.22% | 1.10 | 31.58% | 27.69% | 0.18 |
SPTLC3 | 81.45% | 87.50% | 0.78 | 87.18% | 81.25% | 0.62 | 91.46% | 83.33% | 1.69 | 94.74% | 84.62% | 2.39 |
DENND5B | 0.00% | 0.00% | 0.00 | 0.00% | 0.00% | 0.00 | 2.44% | 2.78% | 0.01 | 2.63% | 1.54% | 0.15 |
KLC1 | 3.23% | 7.50% | 1.35 | 2.56% | 4.69% | 0.29 | 0.00% | 0.00% | 0.00 | 0.00% | 0.00% | 0.00 |